Mumps virus (MuV), a paramyxovirus, causes acute parotitis in humans, characterized by lateral or bilateral swelling of the salivary glands. MuV is also notable as a highly neurotropic and neurovirulent agent causing a number of central nervous system (CNS) manifestations ranging from mild meningitis to severe, and occasionally fatal, encephalitis. Mumps virus infection was the most common cause of viral meningitis and encephalitis until the arrival of mass immunization with mumps virus vaccine. The incidence of mumps and its complications were dramatically reduced following the introduction of measles, mumps, rubella vaccine (MMR) in 1971. MMR vaccine containing the Jeryl Lynn (JL) strain, an attenuated strain of MuV, is highly efficacious and produces few adverse reactions. Currently, mumps virus vaccination is a part of a two dose MMR (mumps, measles, and rubella) vaccine regimen that is administrated to children at one and five years of age in the United States.
In recent years, MuV has caused epidemics among highly vaccinated populations. In 2006, the U.S. experienced the largest mumps epidemic in nearly 20 years (Marin et al., 2008, Vaccine; 26(29-30):3601-3607). The outbreak originated at a university in Iowa and spread to eleven other states. Over 5000 mumps cases were reported in 2006 compared to an average of approximately 250 cases/year in the previous decade. In 2009-2010, a mumps outbreak occurred in the State of New York and the State of New Jersey in the US in which 88% of the patients had one-dose of mumps vaccine and 75% of the patients had two doses of vaccine (MMWR Morb Mortal Wkly Rep; 59(5):125-129, 2010).
While definitive causes for these recent outbreaks are not known, possible reasons (not mutually exclusive) for these outbreaks include waning immunity, high velocity of infection, and vaccine failure due to emerging of a new mumps virus strain. See, for example, (Crowley and Afzal, 2002, Commun Dis Public Health; 5(4):311-313; Lim et al., 2003, J Med Virol; 70(2):287-292; Otto et al., 2010, Euro Surveill; 15(50); Strohle et al., 1996, Arch Virol; 141(3-4):733-741; Utz et al., 2004, J Med Virol; 73(1):91-96; and Whelan et al., 2010, Euro Surveill; 15(17). The results of a large study to examine the efficacy of the two-dose MMR against mumps virus by CDC indicate that titers of anti-MuV dropped dramatically 12 years after the second dose of MMR (17 years of age), to the level of pre-second dosage inoculation. Furthermore, neutralizing antibody titers are low in adults: out of 101 sera tested, 74 were positive using ELISA and only one had neutralization antibody titer higher than 1:8. This is consistent with the fact that in the 2006 outbreak, the most affected population was 18 to 24 years of age. In the 2010 outbreak, most affected patients were 13 to 14 years of age. Both recent outbreaks occurred in high-density populations (college campus and religious school). High velocity infection (for example, large quantity of infectious virions transmitted from one to another due to close contact) may have overwhelmed the anti-MuV immunity in recent outbreaks.
The current vaccine Jeryl Lynn (JL) is based in MuV genotype A, while recent outbreaks have been caused by genotype G. It is possible that vaccine generated immunity based on strain A is ineffective in preventing infection of strain G, leading to the outbreak. Because of re-emerging of mumps virus outbreaks even in vaccinated populations, mumps virus has been listed as a high priority pathogen by National Institute of Allergy and Infectious Diseases (see “Emerging and Re-emerging Infectious Diseases” on the worldwide web at niaid.nih.gov/topics/emerging/list.htm). Currently, live attenuated MuV vaccines are obtained through serial passages in embryonic eggs and cells. This is a time consuming process and a strategy with a poor record of generating safe vaccines.
Thus, there is a need for new and improved mumps vaccines, including the development of vaccines directed at the genotype G and a need for new and improved methods for developing mumps vaccines.